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Acute Myeloid LeukemiaPhase 1NCT04155580

A Study of ASTX660 as a Single Agent and in Combination With ASTX727 in Subjects With Relapsed/Refractory Acute Myeloid Leukemia (AML)

A Phase 1 study testing ASTX660 and ASTX727 in people with Acute Myeloid Leukemia, run by Astex Pharmaceuticals, Inc. at 15 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

To evaluate the safety, pharmacokinetics (PK), and efficacy of ASTX660 when given alone and in combination with ASTX727 in participants with relapsed/refractory (R/R) acute myeloid leukemia (AML). The duration of the study is expected to be approximately 30 months. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
ASTX660 and ASTX727
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
68 participants
Where
15 sitesUnited States
Study dates
12 Jun 2020to 14 Jan 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Have a projected life expectancy of at least 12 weeks, as assessed by the Investigator.
  • Have histological confirmation of AML by World Health Organization (WHO) 2016 criteria and are either:
  • refractory to intensive induction chemotherapy OR
  • relapsed after intensive induction chemotherapy or stem cell transplant OR
  • relapsed after or refractory to treatment with molecularly targeted and/or low-intensity chemotherapeutic regimens.
  • Have an Eastern Cooperative Oncology Group (ECOG) Performance status of 0 to 2.
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  • Have adequate renal function as demonstrated by measured or calculated creatinine clearance ≥60 mL/min.
  • Have adequate liver function as demonstrated by:
  • Aspartate aminotransferase (AST) ≤2.5 × upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) ≤2.5 × ULN
  • Bilirubin ≤1.5 × ULN - unless considered due to leukemic organ involvement.
  • Women of child-bearing potential (according to recommendations of the Clinical Trial Facilitation Group [CTFG]) must not be pregnant or breastfeeding and must have a negative pregnancy test at screening.

Who cannot join

  • Poor medical risk in the investigator's opinion because of systemic diseases in addition to the cancer under study, for example, uncontrolled infections.
  • Known clinically active central nervous system (CNS) leukemia.
  • BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis).
  • Diagnosis of acute promyelocytic leukemia (M3 AML or APML).
  • Second malignancy currently requiring active therapy, except breast or prostate cancer stable on or responding to endocrine therapy.
  • Graft Versus Host Disease (GVHD), or any GVHD requiring treatment with immunosuppression. Any GVHD treatment (including calcineurin inhibitors) must be discontinued at least 28 days prior to Day 1 of study treatment.
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  • Presence of persistent toxicities of Grade >1 from prior treatment including chemotherapy, targeted therapy, immunotherapy, experimental agents, radiation, and surgery (except for alopecia).
  • Hypersensitivity to decitabine, ASTX727, ASTX660, or any of their excipients.
  • Liver cirrhosis, or chronic liver disease Child-Pugh Class B or C.
  • Life-threatening illness, significant organ system dysfunction, or other condition that, in the investigator's opinion, could compromise participant safety, or the integrity of study outcomes, or interfere with the absorption or metabolism of ASTX660 or ASTX727.
  • History of, or at risk for, cardiac disease.
  • Known human immunodeficiency virus (HIV), active hepatitis B virus (HBV), or active hepatitis C virus (HCV) infection (participants with laboratory evidence of no active replication will be permitted).
  • Known significant mental illness or other conditions, such as active alcohol or other substance abuse that, in the opinion of the investigator, predispose the participant to high risk of noncompliance with the protocol treatment or assessments.
  • Treated with any investigational therapy within 2 weeks of the first dose of study treatment or treatment with a myelosuppressive therapy within 4 weeks of the first dose of study treatment.
  • In Parts 1 and 2, prior treatment with decitabine for more than 2 cycles. In Part 3, any treatment with an HMA (azacitidine or decitabine, for more than one cycle).
  • Inability to swallow oral medication or inability or unwillingness to comply with the administration requirements related to ASTX660-02 (Note: G-tube administration is not allowed).

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

United States15 sites

  • Northside Hospital - The Blood and Marrow Transplant Group of Georgia

    Atlanta, Georgia, 30342

  • Roswell Park Comprehensive Cancer Center

    Buffalo, New York, 14263

  • Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • The University of Chicago Medical Center

    Chicago, Illinois, 60637

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • The University of Kansas Clinical Research Center

    Fairway, Kansas, 66205

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Franciscan Health Indianapolis (Blood and Marrow Transplantation)

    Indianapolis, Indiana, 46237

  • Sylvester Comprehensive Cancer Center

    Miami, Florida, 33136

  • Vanderbilt - Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Smilow Cancer Hospital

    New Haven, Connecticut, 06510

  • New York University Langone Health

    New York, New York, 10016

  • Mount Sinai Medical Center

    New York, New York, 10029

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • University of California San Francisco

    San Francisco, California, 94143

Other trials in United States

About this study

Official title: A Phase 1, Parallel, Open-Label Study of the Safety and Tolerability, Pharmacokinetics, and Antileukemic Activity of ASTX660 as a Single Agent and in Combination With ASTX727 in Subjects With Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML)

To evaluate the safety, pharmacokinetics (PK), and efficacy of ASTX660 when given alone and in combination with ASTX727 in participants with relapsed/refractory (R/R) acute myeloid leukemia (AML). The duration of the study is expected to be approximately 30 months.

Read the detailed description

This is a three-part dose escalation and dose expansion Phase 1 study of ASTX660 alone and in combination with ASTX727 in adults with R/R AML.

Part 1 is an open-label, single arm, dose escalation with ASTX660 in combination with ASTX727 at the standard fixed dose combination (FDC).

Part 2 is an open-label, randomized, dose escalation intended to evaluate ASTX660 as a monotherapy and ASTX660 in combination with ASTX727 FDC.

Part 3 is an exploratory single arm dose expansion to further expand the number of participants treated with ASTX660 in combination with ASTX727 FDC.

Being tested
ASTX660, ASTX727
Keywords
AML, Bone marrow, CMML, MDS, ASTX727, ASTX660, cIAP1, Cellular inhibitor of apoptosis protein, XIAP, CDAi, Cytidine deaminase inhibitor, Cedazuridine, Decitabine, Acute myeloid leukemia, Chronic myelomonocytic leukemia, Myelodysplastic syndrome
Medical subject headings
Leukemia, Myeloid, Acute, Leukemia, Myelomonocytic, Chronic, Myelodysplastic Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ASTX660Drug

    Capsule for oral administration

  • ASTX727Drug

    Also called cedazuridine + decitabine

    Tablet for oral administration

Study groups in NCT04155580
Study groupRoleWhat they receive
Part 1ExperimentalASTX660 once daily (Days 1-7 and 15-21 per 28-day cycle) + ASTX727 FDC once daily (Days 1-5 per 28-day cycle)
Receives: Drug: ASTX660; Drug: ASTX727
Part 2ExperimentalASTX660 once daily (Days 1-7 and 15-21 per 28-day cycle) as a single agent or in combination with ASTX727 FDC once daily (Days 1-5 per 28-day cycle)
Receives: Drug: ASTX660; Drug: ASTX727
Part 3ExperimentalASTX660 at the recommended dose for expansion identified in Part 2 + ASTX727 FDC once daily (Days 1-5 per 28-day cycle)
Receives: Drug: ASTX660; Drug: ASTX727

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety Assessment: Number of participants with treatment-emergent adverse events (TEAEs)

    Measured: Up to 30 months

Secondary outcomes (11)

  1. Response rate: Number of participants achieving complete response (CR), complete response with incomplete hematological recovery (CRi), and partial response (PR) as determined by the European LeukemiaNet (ELN) 2017 response criteria for AML

    Measured: Up to 30 months

  2. Time to response: Time from first dose to the first documented evidence of response

    Measured: Up to 30 months

  3. Duration of response: Time from the start of response until disease progression or relapse

    Measured: Up to 30 months

  4. Overall survival: Time since first dose until death due to any cause

    Measured: Up to 30 months

  5. Composite complete response: Number of participants (sum of CR+CRi)

    Measured: Up to 30 months

  6. Complete response with partial hematological recovery (CRh): Number of participants

    Measured: Up to Month 30

  7. Pharmacokinetic parameter: Area under the curve (AUC)

    Measured: On Days 1, 5 and 6 of Cycle 1 and Day 1 of Cycle 2 (28 days per cycle)

  8. Pharmacokinetic parameter: Maximum plasma concentration (Cmax)

    Measured: On Days 1, 5 and 6 of Cycle 1 and Day 1 of Cycle 2 (28 days per cycle)

  9. Pharmacokinetic parameter: Minimum plasma concentration (Cmin)

    Measured: On Days 1, 5 and 6 of Cycle 1 and Day 1 of Cycle 2 (28 days per cycle)

  10. Pharmacokinetic parameter: Time to reach maximum plasma concentration (Tmax)

    Measured: On Days 1, 5 and 6 of Cycle 1 and Day 1 of Cycle 2 (28 days per cycle)

  11. Pharmacokinetic parameter: Half-life (t½)

    Measured: On Days 1, 5 and 6 of Cycle 1 and Day 1 of Cycle 2 (28 days per cycle)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Nov 2019
  2. Study start12 Jun 2020
  3. Primary completion14 Jan 2022
  4. Study completion14 Jan 2022

Why it stopped: Study halted prematurely and will not resume; participants are no longer being examined or receiving intervention

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
68 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04155580
Sponsor's protocol ID
ASTX660-02
Status last verified
Aug 2024
First submitted
5 Nov 2019
Last updated
2 Aug 2024
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ASTX660 and ASTX727 in people with Acute Myeloid Leukemia, run by Astex Pharmaceuticals, Inc. at 15 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 2 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Study halted prematurely and will not resume; participants are no longer being examined or receiving intervention). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety Assessment: Number of participants with treatment-emergent adverse events (TEAEs) (time frame: Up to 30 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04155580.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Aug 2024.

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Clinical Trial NCT04155580 | AzTrials